Research is directed at understanding the cellular and genetic events that control normal T cell development. Transgenic and gene-targeting methods are used to analyze the function of specific genes in development and various molecular techniques (eg., gene cloning and PCR) are being employed to identify novel genes that participate in thymocyte development. Current studies focus on the role of the T cell antigen receptor (TCR) in thymocyte maturation. The TCR is responsible for antigen recognition, T cell activation and cell mediated immunity. In addition, the TCR plays a critical role in thymocyte development and thymic selection. How the TCR is capable of orchestrating these events remains a central question in developmental immunology. The TCR is composed of multiple signal transducing subunits (the CD3 chains and one or more members of the zeta-family of proteins). Each of these subunits contains sequences that couple the TCR to intracellular signal transduction pathways. To address whether the TCR subunits perform distinct or analogous functions in development several experimental approaches have been taken: a) the function of individual TCR subunits has been examined by overexpression in transgenic mice; b) the role of zeta-chain signaling motifs or of other zeta-family proteins in thymocyte development is bring addressed by transgene-reconstitution of zeta-deficient mice. These studies have led to 2 major findings: 1) Expression of zeta chain (or related protein) is required for TCR expression and consequently for normal T cell development. However, surprisingly, signals transduced by zeta are to absolutely required for T cell development. Thus the CD3 module of the TCR is sufficient to transduce all of the signals necessary for thymocyte maturation. 2) Individual signal transducing molecules (i.e., the CD3 chains and the zeta-family proteins) function at different stages of development, presumably as subunits of distinct signaling complexes. The composition of these complexes and their function in development is under investigation.